Schizophrenia copy number variants and associative learning.

Large-scale genomic studies have made major progress in identifying genetic risk variants for schizophrenia. A key finding from these studies is that there is an increased burden of genomic copy number variants (CNVs) in schizophrenia cases compared with controls. The mechanism through which these CNVs confer risk for the symptoms of schizophrenia, however, remains unclear. One possibility is that schizophrenia risk CNVs impact basic associative learning processes, abnormalities of which have long been associated with the disorder. To investigate whether genes in schizophrenia CNVs impact on specific phases of associative learning we combined human genetics with experimental gene expression studies in animals. In a sample of 11 917 schizophrenia cases and 16 416 controls, we investigated whether CNVs from patients with schizophrenia are enriched for genes expressed during the consolidation, retrieval or extinction of associative memories. We show that CNVs from cases are enriched for genes expressed during fear extinction in the hippocampus, but not genes expressed following consolidation or retrieval. These results suggest that CNVs act to impair inhibitory learning in schizophrenia, potentially contributing to the development of core symptoms of the disorder.

Implant-specific follow-up imaging of treated intracranial aneurysms: TOF-MRA vs. metal artifact reduced intravenous flat panel computed tomography angiography (FPCTA).

AIM: To compare the diagnostic quality of time-of-flight magnetic resonance angiography (TOF-MRA) and metal-artefact-reduction (MAR) flat-panel-detector computed tomography angiography (FPCTA) and to determine the imaging technique best suited for evaluation endovascular and surgically treated aneurysms. METHODS: The image quality of TOF-MRA and MAR-FPCTA of 44 intracranial implants (coiling: n=20; clipping: n=15; coiling + stenting: n=9) in a patient cohort of 25 was evaluated by two independent readers. Images obtained using MAR-FPCTA (20 second scan time, 496 projections, intravenous contrast medium administration; Artis Zee, Siemens Healthcare, Forchheim) were compared with TOF-MRA-images (1.5 or 3 T). Nominal data were analysed using McNemar's chi-square test and ordinal variables using the Wilcoxon rank test. RESULTS: Compared to TOF-MRA, MAR-FPCTA was significantly better suited to detect aneurysm remnants and to evaluate parent vessels after clipping (p<0.01). For coil packages >160 mm3, TOF-MRA provided significantly better assessment than MAR-FPCTA (p<0.01). For small coil packages (<160 mm3), no significant difference between TOF-MRA and MAR-FPCTA (p=0.232) was observed. For different clip sizes (cut-off 492 mm3) likewise no significant differences were found. The interobserver comparison showed high interrater agreement. CONCLUSION: MAR-FPCTA is significantly better suited for follow-up examinations of clipped aneurysms, whereas for larger coil packages TOF-MRA is preferable. Smaller coil packages can be analysed using MAR-FPCTA or TOF-MRA.

Dustbathing in food particles does not remove feather lipids.

Within the European Union, dustbathing material in cage-housing systems for laying hens became compulsory in 2012. In practice, most producers use food particles as litter substrate. The feed is dropped in small amounts on scratching mats by an automatic transporting system. However, because dustbathing behavior is meant to remove stale lipids from hens' plumage, food particles may not be a suitable substrate due to their fat content. This study analyzes feather lipid concentration (FLC) of laying hens with access to food particles (F) or lignocellulose (L) as litter substrates. In each of 2 identical trials, 84 laying hens of 2 genotypes (Lohmann Selected Leghorn, Lohmann Brown) were kept in 12 compartments (7 hens each). Compartments were equipped with a grid floor and additionally contained a closed dustbathing tray holding F or L. Feather samples (150 feathers) were taken 2 times throughout the experiment. At 23 wk of age, 4 hens per compartment were sampled after they were allowed pair-wise access to a dustbath for 2.5 h and 3 hens were sampled without access to a dustbathing tray (control). After 10 wk of free access to the dustbathing trays, all hens were sampled again. In trial 2, an additional third sampling was made after dustbaths had been closed again for 6 wk. Here, 6 hens per compartment were sampled immediately before and after a dustbath. Dustbathing in F resulted in higher FLC compared with L and control (P < 0.001), whereas no significant difference was found between L and control (P = 0.103). When open access to litter was provided, hens had higher FLC in F compared with L (P < 0.001). The FLC immediately after dustbathing in F was higher compared with the level before dustbathing (P < 0.001), whereas it was lower after dustbathing in L (P = 0.006). These results show that F are not suitable litter material for laying hens because they lead to lipid accumulation on the plumage.

Analysis of landing behaviour of three layer lines on different perch designs.

1. The prevalence of keel bone deformities in laying hens is high and is partly associated with unsuitable perch designs, which impose a risk of injury due to an unstable footing. 2. Over two experiments, 9 or 10 hens of each of three layer lines (Lohmann Selected Leghorn (LSL), Lohmann Tradition (LT) and Lohmann Brown (LB)) were filmed while landing on three different perch types, including steel perches of various diameters, a commercial mushroom-shaped plastic perch and a newly developed prototype perch with a soft surface material. 3. Data on landing behaviour (safe vs. unsafe or failed landing) following downward jumps were collected for 25, 50 and 60 cm vertical distances and 75 cm horizontal distance between a wooden start perch and the different destination perches. 4. The highest proportion of safe landings occurred on the prototype perch, whereas least safe landings were observed on steel perches, irrespective of their diameter. The mushroom-shaped perch was intermediate with regard to the safeness of landing. 5. A threshold of 50 cm vertical distance (34° slope) was identified as the optimum for downward jumps on perches in order to reduce the risk of unsafe or failed landings. Above this threshold, the proportion of safe landings declined significantly. 6. Brown shell layer types (LB and LT) had a lower proportion of safe landings compared to the white shell layer type (LSL), whereas no difference was found between LB and LT layer lines. 7. Although steel perches prevail in commercial housing, these perches were found to be least advantageous with regard to landing behaviour. The prototype perch provided the most stable footing on perching and is a promising alternative to replace commercial steel perches, thus helping to reduce the risk of perch-related keel bone injury.

Pressure load on keel bone and foot pads in perching laying hens in relation to perch design.

The provision of perches in housing systems for laying hens is meant to improve hens' welfare by allowing a more natural behavior repertoire. However, the use of perches is associated with welfare problems, such as keel bone deviations and foot pad lesions, that may possibly result from high mechanical pressure load during extended perching activities. The aim of this study was to analyze peak force and contact area of hens' keel bones and foot pads on solid test perches of square, round, and oval shape with 3 different diameters each (experiment 1) and on commercially used perches (round steel tube, 2 sizes of mushroom-shaped plastic, and flattened round plastic) together with 2 prototypes of soft, round polyurethane perches (experiment 2). Test perches were covered with a pressure sensor film and 36 laying hens (18 Lohmann Selected Leghorn, 18 Lohmann Brown) were consecutively placed on each perch in an experimental cage during nighttime. Peak force (N/cm(2)) and contact area (cm(2)) were measured while hens were sitting and standing on the different test perches. Pressure peaks on the keel bone were approximately 5 times higher compared with single foot pad. On square perches, keel bone peak force was lower (P < 0.05) and contact area was larger (P < 0.001) compared with round and oval perches. In addition, peak force on foot pads in standing hens was higher on square perches (P < 0.05) compared with oval perches. Perch size did not affect peak forces on keel bones in sitting hens and foot pads in standing hens (experiment 1). On prototype perches, peak force on the keel bone was lower and contact area was larger compared with all commercial perches tested (P < 0.001). Peak force on foot pads was lower on prototype perches compared with steel perches (P < 0.01; experiment 2). Perches with a soft surface may possibly reduce keel bone and foot pad welfare problems in perching laying hens.

Litter lipid content affects dustbathing behavior in laying hens.

Within the European Union, the provision of dustbathing material in layer housing systems will be compulsory beginning in 2012. In cage systems, food particles are mainly used as litter material and are provided on scratching mats by an automatic transporting system. However, because dustbathing is a means for hens to remove stale lipids from their plumage, lipid content of a substrate may be an important asset with regard to its adequacy. This study analyzes dustbathing behavior as affected by lipid content of feed used as litter material. A total of 72 laying hens of 2 genotypes (Lohmann Selected Leghorn, Lohmann Brown) were kept in 12 compartments (6 hens each). Compartments were equipped with a plastic grid floor (G) and additionally contained 3 different dustbathing trays (each 1,000 cm(2)/hen) holding low-lipid (0.82%; L), normal-lipid (4.2%; N), and high-lipid (15.7%; H) food particles. The experiment began at 20 wk of life, and video recordings were done at wk 23, 26, and 29. Number of dustbaths, time spent dustbathing, average dustbath duration, foraging, and single behaviors within dustbaths were analyzed during the light period over 2 d in each observation week. Dustbaths occurred most frequently in the L compared with the N, H, and G treatments (all P < 0.001). Total time spent dustbathing was longest in the L treatment compared with the N and H treatments (P < 0.001). No difference in the average duration of single dustbaths was found between the L, N, and H treatments. However, when dustbath interruptions (less than 10 min) were excluded, the duration of single dustbaths was longer in the H compared with the L (P = 0.009) and N (P = 0.024) treatments. Foraging was most frequently observed in the N compared with the L, H, and G treatments (all P < 0.001). More body wing shakes occurred in the L compared with the N treatment, and the number of vertical wing shakes was higher in the N compared with the H treatment (all P ≤ 0.05). Our results showed that preference for a dustbathing substrate increased with decreasing lipid content, implying that food particles may not be a suitable dustbathing substrate.

Reducing stress during welfare inspection: validation of a non-intrusive version of the LayWel plumage scoring system for laying hens.

1. The objectives of the present study were to validate a reduced, non-intrusive version (RLS) of the LayWel plumage scoring system in domestic laying hens with reference to complete, intrusive scoring (CLS) and to investigate the effect of these two scoring methods on corticosterone metabolite concentrations. 2. A total of 312 medium-heavy laying hens from 4 commercial hybrids kept in 24 floor pens were scored by two experienced teams. Another 150 hens from two hybrids kept in 6 pens were used for estimating scoring treatment effects on corticosterone metabolites in droppings. 3. Plumage scores were in general higher using the RLS method compared to the CLS method. The agreement between teams for plumage scores (CLS) were on a high (total score) to an excellent (single body part except breast and cloaca) level. 4. Birds subjected to CLS tended to have higher concentrations of corticosterone metabolites in droppings 2 h after scoring compared with birds in the control treatment (not scored). Birds subjected to RLS had intermediate concentrations. 5. It was concluded that a reduced version of the LayWel scoring system is a valid and reliable scoring method which tends to induce less stress to the subjects than the original procedure.

Sirolpidium bryopsidis, a parasite of green algae, is probably conspecific with Pontisma lagenidioides, a parasite of red algae.

The genus Sirolpidium (Sirolpidiaceae) of the Oomycota includes several species of holocarpic obligate aquatic parasites. These organisms are widely occurring in marine and freshwater habitats, mostly infecting filamentous green algae. Presently, all species are only known from their morphology and descriptive life cycle traits. None of the seven species classified in Sirolpidium, including the type species, S. bryopsidis, has been rediscovered and studied for their molecular phylogeny, so far. Originally, the genus was established to accommodate all parasites of filamentous marine green algae. In the past few decades, however, Sirolpidium has undergone multiple taxonomic revisions and several species parasitic in other host groups were added to the genus. While the phylogeny of the marine rhodophyte- and phaeophyte-infecting genera Pontisma and Eurychasma, respectively, has only been resolved recently, the taxonomic placement of the chlorophyte-infecting genus Sirolpidium remained unresolved. In the present study, we report the phylogenetic placement of Sirolpidium bryopsidis infecting the filamentous marine green algae Capsosiphon fulvescens sampled from Skagaströnd in Northwest Iceland. Phylogenetic reconstructions revealed that S. bryopsidis is either conspecific or at least very closely related to the type species of Pontisma, Po. lagenidioides. Consequently, the type species of genus Sirolpidium, S. bryopsidis, is reclassified to Pontisma. Further infection trials are needed to determine if Po. bryopsidis and Po. lagenidioides are conspecific or closely related. In either case, the apparently recent host jump from red to green algae is remarkable, as it opens the possibility for radiation in a largely divergent eukaryotic lineage. Citation: Buaya AT, Scholz B, Thines M (2021). Sirolpidium bryopsidis, a parasite of green algae, is probably conspecific with Pontisma lagenidioides, a parasite of red algae. Fungal Systematics and Evolution 7: 223-231. doi: 10.3114/fuse.2021.07.11.

Neuroimaging Features of Ectopic Cerebellar Tissue: A Case Series Study of a Rare Entity.

Ectopic cerebellar tissue is a rare entity likely secondary to multiple, interacting, developmental errors during embryogenesis. Multiple sites of ectopic cerebellar tissue have been reported, including extracranial locations; however, an intracranial location is most common. We report on the MR imaging findings of a multi-institutional series of 7 ectopic cerebellar tissue cases (2 males, 4 females, 1 fetal) ranging from 22 weeks 5 days' gestational age to 18 years of age. All cases of ectopic cerebellar tissue were diagnosed incidentally, while imaging was performed for other causes. Ectopic cerebellar tissue was infratentorial in 6/7 patients and supratentorial in 1/7 patients. All infratentorial ectopic cerebellar tissue was connected with the brain stem or cerebellum. MR imaging signal intensity was identical to the cerebellar gray and white matter signal intensity on all MR imaging sequences in all cases. Ectopic cerebellar tissue should be considered in the differential diagnoses of extra-axial masses with signal characteristics similar to those of the cerebellum. Surgical biopsy or resection is rarely necessary, and in most cases, MR imaging is diagnostic.

Suppression of adverse angiogenesis in an albumin-based hydrogel for articular cartilage and intervertebral disc regeneration.

An injectable polyethylene glycol-crosslinked albumin gel (AG) supplemented with hyaluronic acid as a matrix for autologous chondrocyte implantation was evaluated with regard to its impact on angiogenesis. Healthy articular cartilage and intervertebral discs (IVD) are devoid of blood vessels, whereas pathological blood vessel formation augments degeneration of both theses tissues. In contrast to human endothelial cells, primary human articular chondrocytes encapsulated in the AG retained their viability. Endothelial cells did not adhere to the gel surface to a significant extent nor did they proliferate in vitro. The AG did not release any diffusible toxic components. Contrary to Matrigel employed as positive control, the AG prevented endothelial chemoinvasion in Transwell filter assays even in the presence of a chemotactic gradient of vascular endothelial growth factor. In ovo, the AG exhibited a barrier function for blood vessels of the chick chorioallantoic membrane. Subcutaneous implantation of human IVD chondrocytes enclosed in the albumin gel into immunodeficient mice revealed a complete lack of angiogenesis inside the gel after two weeks. At the same time, the IVD chondrocytes within the gel remained vital and displayed a characteristic gene expression pattern as judged from aggrecan, collagen type I and type II mRNA levels. In summary, aiming at articular cartilage and IVD regeneration the albumin gel promises to be a beneficial implant matrix for chondrocytes simultaneously exhibiting non-permissive properties for adverse endothelial cells.

Food, wood, or plastic as substrates for dustbathing and foraging in laying hens: A preference test.

The provision for dustbathing material will be a legal requirement in cage-housing systems for laying hens within the European Union beginning in 2012. At present, food particles are widely used and typically offered in small amounts on Astroturf mats one or more times per day to facilitate dustbathing, pecking, and scratching. In the present study, we compared layers' preference for food and 3 other (nonnutritive) substrates for foraging and dustbathing. In each of 2 identical trials, 72 hens of 2 genotypes (Lohmann Selected Leghorn and Lohmann Brown) were kept in 12 compartments (6 hens each). Compartments were equipped with a plastic grid floor and additionally contained 4 different dustbathing trays (each 1,000 cm(2)/hen) holding either wood shavings (WS), lignocellulose (LN, soft wood fiber, pelleted), Astroturf mat without substrate (AT), or food particles (FP). Hens were housed from 18 wk of age and video recordings were done at wk 21, 24, and 27. Time spent and frequency of dustbathing, duration of a single dustbath (DB), frequency of foraging behavior, and relative frequency and duration of behavioral patterns within a single DB were recorded during the light period over 2 d in each observation week. The FP treatment was preferred for foraging over WS, LN, and AT. Time spent dustbathing and number of DB were higher in LN compared with WS, FP, and AT, whereas average duration of a single DB was longer in FP compared with LN and WS. More vertical wing shakes and scratching bouts within a single DB were observed in LN compared with AT. Bill raking occurred more frequently in WS and LN in comparison to FP and AT. No differences in the relative durations of behavioral patterns within a single DB were found. In conclusion, FP were preferred for foraging but not for dustbathing, indicating that FP may not be an optimal dustbathing substrate for laying hens.

CREM-transgene mice: An animal model of atrial fibrillation and thrombogenesis.

BACKGROUND: The molecular pathomechanisms underlying atrial thrombogenesis are multifactorial and still require detailed investigations. Transgenic mice with cardiomyocyte-directed expression of the transcriptional repressor CREM-IbΔC-X (CREM-TG) represent an experimental model of atrial fibrillation (AF) that shows a gradual, age-dependent progression from atrial ectopy to persistent AF. Importantly, this model develops biatrial thrombi. The molecular characteristics related to the thrombogenesis in CREM-TG mice have not been studied, yet. METHODS: The inflammatory and prothrombotic state was evaluated at the transcriptional (qRT-PCR) and protein level in the left (LA) and right atria (RA) from CREM-TG mice at the age of 20weeks and compared to wild-type controls. Moreover, histological analyses of atrial thrombi were performed. RESULTS: The endocardial dysfunction was mirrored by diminished levels of eNOS-mRNA in both atria (RA: 0.79±0.04, LA: 0.72±0.06; each P<0.05). Moreover, the PAI-1/t-PA mRNA ratio was significantly increased in both atria (RA: 3.6±0.6; P<0.01, LA: 4.0±1.0; P<0.05) indicating a high risk of thrombus formation. However, the inflammatory phenotype was more pronounced in the RA and was reflected by a significant increase in the mRNA levels encoding adhesion molecules ICAM-1 (2.1±0.2; P<0.01), VCAM-1 (2.3±0.5; P<0.05), and selectin P (3.6±0.5: P<0.05). CONCLUSIONS: CREM-TG mice represent a valuable model for studying atrial thrombogenesis and assessing therapeutic approaches preventing embolic events in the systemic and pulmonary circulation.

Analysis of the influences on plumage condition in laying hens: How suitable is a whole body plumage score as an outcome?

An important indicator of the health and behavior of laying hens is their plumage condition. Various scoring systems are used, and various risk factors for feather damage have been described. Often, a summarized score of different body parts is used to describe the overall condition of the plumage of a bird. However, it has not yet been assessed whether such a whole body plumage score is a suitable outcome variable when analyzing the risk factors for plumage deterioration. Data collected within a German project on farms keeping laying hens in aviaries were analyzed to investigate whether and the extent to which information is lost when summarizing the scores of the separate body parts. Two models were fitted using multiblock redundancy analysis, in which the first model included the whole body score as one outcome variable, while the second model included the scores of the individual body parts as multiple outcome variables. Although basically similar influences could be discovered with both models, the investigation of the individual body parts allowed for consideration of the influences on each body part separately and for the identification of additional influences. Furthermore, ambivalent influences (a factor differently associated with 2 different outcomes) could be detected with this approach, and possible dilutive effects were avoided. We conclude that influences might be underestimated or even missed when modeling their explanatory power for an overall score only. Therefore, multivariate methods that allow for the consideration of individual body parts are an interesting option when investigating influences on plumage condition.

Recombination between adenovirus type 12 DNA and a hamster preinsertion sequence in a cell-free system. Patch homologies and fractionation of nuclear extracts.

We have previously described a cell-free recombination system derived from hamster cell nuclear extracts in which the in vitro recombination between a hamster preinsertion sequence, the cloned 1768 base-pair p7 fragment, and adenovirus type 12 (Ad12) DNA has been demonstrated. The nuclear extracts have now been subfractionated by gel filtration on a Sephacryl S-300 column. The activity promoting cell-free recombination elutes from the Sephacryl S-300 matrix with the shoulder and not the peak fractions of the absorbancy profile. By using these protein subfractions, in vitro recombinants have been generated between the p7 preinsertion sequence and the 60 to 70 map unit fragment of Ad12 DNA, which has previously shown high recombination frequency. In all of the analyzed recombinants thus produced in vitro, striking patchy homologies have been observed between the p7 and Ad12 junction sequences, and between Ad12 DNA or p7 DNA and pBR322 DNA. The patchy homologies are similar to those found earlier during the analyses of some of the junction sequences in integrated Ad12 genomes in Ad12-induced hamster tumor cell lines. Proteins in the shoulder fractions of the gel-filtration experiment can form specific complexes with double-stranded synthetic oligodeoxyribonucleotides corresponding to several p7 and Ad12 DNA sequences. These sequences participate in the recombination reactions catalyzed by the same column fractions in the shoulder of the absorbancy profile. Such proteins have not been found in the peak fractions. Further work will be required to ascertain that the cell-free recombination system mimics certain elements of the mechanisms of integrative recombination and to purify the cellular components essential for recombination.

Duration of vitrectomy and postoperative cataract in the vitrectomy for macular hole study.

PURPOSE: To report the association between duration of vitrectomy, as well as other risk factors, and the progression of nuclear sclerosis and posterior subcapsular cataract in the Vitrectomy for Macular Hole Study. DESIGN: A cohort study nested within a randomized controlled clinical trial. METHODS: Using a system similar to the Lens Opacities Classification System II, nuclear sclerosis (NS) and posterior subcapsular cataract (PSC) were scored in the vitrectomy and fellow eye of 74 patients at baseline and at 6, 12, and 24 months postoperatively. Age, baseline blood pressure and refractive power, and duration of surgery were evaluated as risk factors for NS or PSC progression and cataract extraction. RESULTS: The incidence of NS progression in the surgical group of vitrectomy eyes was 81% at 6 months, 98% at 1 year, and 100% at 2 years of follow-up. In contrast, NS progression in the control group of fellow eyes was only 18% at 6 months, 20% at 1 year, and 8% at 2 years. The incidence of PSC progression in the surgical group remained at approximately 11% throughout follow-up, which was not significantly higher than the 3% to 5% incidence in the control group. Vitrectomy was significantly related to progression of NS cataract (P <.001) and cataract extraction (P <.01). No statistically significant differences were found for NS scores, PSC scores, or progression rates between eyes that had less than median surgical duration (60 min.) or more than the median surgical duration. Additionally, no significant differences were found when eyes that experienced 45 minutes or less surgical duration were compared with eyes that endured more than 75 minutes surgical duration. Age, blood pressure, and refractive power were not found to be predictors for NS and PSC progression. CONCLUSIONS: Although vitrectomy is a risk factor for NS progression, the duration of vitrectomy does not increase the risk.

Reconstructing current distributions from biomagnetic measurements under large external noise disturbances.

External noise fields cause spatially coherent noise in the biomagnetic data measured by a multichannel magnetometer. The authors propose a method of incorporating this spatial coherence into current-density reconstruction. This method can reconstruct current distributions from biomagnetic measurements affected by external noise fields. Computer simulations demonstrate its effectiveness.

The influence of inhomogeneous volume conductor models on the ECG and the MCG.

The authors investigated the influence of human body inhomogeneities such as the lungs, blood masses and the skeletal muscle layer on the electrical body surface potential and the magnetic field. The surface potentials and magnetic fields are calculated using a boundary element method. As a rule the blood masses have a large influence on both potential and magnetic field amplitude as well as on the potential and magnetic field map orientation, but the influence on the topology of the map is less in the electric case than in the magnetic case. The single-dipole reconstruction was applied to estimate the error caused by neglecting inner inhomogeneities in source localization. The neglect of lungs and blood masses results in a localization error of less than 1 cm in the electric case but more than 1 cm for deep sources at the posterior side of the heart in the magnetic case. The authors tried to assess the influence of the skeletal muscle layer by both an analytical two-layered anisotropic half-space model and the torso extension method. The skeletal muscle layer causes a smoothing effect on the electrical surface potential and to a lesser extent on the magnetic field, leading to an overestimation of the actual source depth of about 1-2 cm. In principle this can be reduced by taking data from all over the thoracic surface. The authors designed experiments for simultaneous measurement of body surface potential and extracorporeal magnetic field from the same subject. The evaluation of data from two patients showing Wolff-Parkinson-White syndrome has shown that localization results from electric potential data and magnetocardiographic data are consistent.

Average-intensity reconstruction and Wiener reconstruction of bioelectric current distribution based on its estimated covariance matrix.

This paper proposes two methods for reconstructing current distributions from biomagnetic measurements. Both of these methods are based on estimating the source-current covariance matrix from the measured-data covariance matrix. One method is the reconstruction of average current intensity distributions. This method first estimates the source-current covariance matrix and, using its diagonal terms, it reconstructs current intensity distributions averaged over a certain time. Although the method does not reconstruct the orientation of each current element at each time instant, it can retrieve information regarding the current time-averaged intensity at each voxel location using extremely low SNR data. The second method is Wiener reconstruction using the estimated source-current covariance matrix. Unlike the first method, this Wiener reconstruction can provide a current distribution with its orientation at each time instant. Computer simulation shows that the Wiener method is less affected by the choice of the regularization parameter, resulting in a method that is more effective than the conventional minimum-norm method when the SNR of the measurement is low.

Generalized Wiener estimation of three-dimensional current distribution from biomagnetic measurements.

This paper proposes a method for estimating three-dimensional (3-D) biocurrent distribution from spatio-temporal biomagnetic data. This method is based on the principle of generalized Wiener estimation, and it is formulated based on the assumption that current sources are uncorrelated. Computer simulation demonstrates that the proposed method can reconstruct a 3-D current distribution where the conventional least-squares minimum-norm method fails. The influence of noise is also simulated, and the results indicate that a signal-to-noise ratio of more than 20 for the uncorrelated sensor noise is needed to implement the proposed method. The calculated point spread function shows that the proposed method has very high spatial resolution compared to the conventional minimum norm method. The results of computer simulation of the distributed current sources are also presented, including cases where current sources are correlated. These results suggest that no serious errors arise if the source correlation is weak.

Probability-based current dipole localization from biomagnetic fields.

Focal biomagnetic sources are described as pointlike current dipoles. The dipole parameters, position, and moment coordinates are commonly determined from biomagnetic data using iterative nonlinear optimization algorithms such as the Levenberg-Marquardt algorithm. However, even for single-dipole sources, mislocalizations can occur due to side minima of the cost function or due to a wrong choice of the start vector. This can be shown by introducing a cost function where the independent variables are only the position coordinates instead of position and moment coordinates. This dimensional reduction--which is also possible for multiple dipole sources--is achieved by calculating the cost function at each position with the position and data-dependent, optimum dipole moments. We call these dipoles with--in a least squares sense--optimum moments, locally optimal dipoles. The visualization of such a single-dipole cost function and of the iteration steps of the Levenberg-Marquardt algorithm show why mislocalizations cannot be avoided. Therefore, we propose an alternative noniterative localization algorithm for single-dipole sources without this drawback. It uses localization probabilities calculated by means of the locally optimal dipoles. Besides the determination of the dipole parameters, the proposed algorithm furnishes a reliable error for each localization. Its effectiveness is shown with simulated and real patient data.